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Operation and performance of the ATLAS semiconductor tracker in LHC Run 2

Aad, Georges ; Abbott, Brad ; Abbott, Dale Charles ; [et al.]

IOP Publishing ; 2022

In: Journal of Instrumentation Vol. 17, No. 01 ( 2022-01-01), p. P01013-

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In: Journal of Instrumentation, IOP Publishing, Vol. 17, No. 01 ( 2022-01-01), p. P01013-

Abstract: The semiconductor tracker (SCT) is one of the tracking systems for charged particles in the ATLAS detector. It consists of 4088 silicon strip sensor modules. During Run 2 (2015–2018) the Large Hadron Collider delivered an integrated luminosity of 156 fb -1 to the ATLAS experiment at a centre-of-mass proton-proton collision energy of 13 TeV. The instantaneous luminosity and pile-up conditions were far in excess of those assumed in the original design of the SCT detector. Due to improvements to the data acquisition system, the SCT operated stably throughout Run 2. It was available for 99.9% of the integrated luminosity and achieved a data-quality efficiency of 99.85%. Detailed studies have been made of the leakage current in SCT modules and the evolution of the full depletion voltage, which are used to study the impact of radiation damage to the modules.

Type of Medium: Online Resource

ISSN: 1748-0221

URL: Article

DOI: 10.1088/1748-0221/17/01/P01013

Language: Unknown

Publisher: IOP Publishing

Publication Date: 2022

detail.hit.zdb_id: 2235672-1

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Three Dimensional Printed Models of Anatomic Variation: A Pilot Study

Lohman Bonfiglio, Chelsea M. ; Richter, Saskia D.

Wiley ; 2020

In: The FASEB Journal Vol. 34, No. S1 ( 2020-04), p. 1-1

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In: The FASEB Journal, Wiley, Vol. 34, No. S1 ( 2020-04), p. 1-1

Type of Medium: Online Resource

ISSN: 0892-6638 , 1530-6860

URL: Issue

URL: Article

DOI: 10.1096/fsb2.v34.S1

DOI: 10.1096/fasebj.2020.34.s1.06818

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 1468876-1

SSG: 12

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Digitalisierung der Arbeit im Gesundheits- und Sozialsektor : Formen, Spannungsfelder und Gestaltungsvoraussetzungen

Evans, Michaela ; Freye, Saskia ; Richter, Caroline

Walter de Gruyter GmbH ; 2020

In: Arbeit Vol. 29, No. 2 ( 2020-06-25), p. 99-104

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In: Arbeit, Walter de Gruyter GmbH, Vol. 29, No. 2 ( 2020-06-25), p. 99-104

Type of Medium: Online Resource

ISSN: 2365-984X , 0941-5025

URL: Article

DOI: 10.1515/arbeit-2020-0008

RVK:

MN 1000

Language: English

Publisher: Walter de Gruyter GmbH

Publication Date: 2020

detail.hit.zdb_id: 2064442-5

detail.hit.zdb_id: 1106284-8

SSG: 3,4

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Application and Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio in Patients with Ischemic and Non-Ischemic Cardiomyopathy

Keranov, Stanislav ; Haen, Saskia ; Vietheer, Julia ; [et al.]

MDPI AG ; 2021

In: Diagnostics Vol. 11, No. 12 ( 2021-11-24), p. 2188-

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In: Diagnostics, MDPI AG, Vol. 11, No. 12 ( 2021-11-24), p. 2188-

Abstract: The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP ( 〈 0.38 mm/mmHg) and TAPSE ( 〈 16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Type of Medium: Online Resource

ISSN: 2075-4418

URL: Article

DOI: 10.3390/diagnostics11122188

Language: English

Publisher: MDPI AG

Publication Date: 2021

detail.hit.zdb_id: 2662336-5

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Safety, Tolerability and 〈i〉Plasmodium Falciparum〈/i〉 Transmission-Reducing Activity of Monoclonal Antibody TB31F: An Open-Label, First-in-Human, Trial in Healthy Malaria-Naïve Adults

van der Boor, Saskia C. ; Smit, Merel ; van Beek, Stijn W. ; [et al.]

Elsevier BV ; 2022

In: SSRN Electronic Journal

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In: SSRN Electronic Journal, Elsevier BV

Type of Medium: Online Resource

ISSN: 1556-5068

URL: Article

DOI: 10.2139/ssrn.4054462

Language: English

Publisher: Elsevier BV

Publication Date: 2022

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Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection

Mhlekude, Baxolele ; Postmus, Dylan ; Stenzel, Saskia ; [et al.]

Public Library of Science (PLoS) ; 2023

In: PLOS Pathogens Vol. 19, No. 9 ( 2023-9-25), p. e1011657-

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In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 9 ( 2023-9-25), p. e1011657-

Abstract: Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant viruses, and reduced viral RNA quantities and infectious titers in the culture supernatant. While we confirmed JQ-1-mediated downregulation of expression of angiotensin-converting enzyme 2 (ACE2) and interferon-stimulated genes (ISGs), multi-omics analysis addressing the chromatin accessibility, transcriptome and proteome uncovered induction of an antiviral nuclear factor erythroid 2-related factor 2 (NRF-2)-mediated cytoprotective response as an additional mechanism through which JQ-1 inhibits SARS-CoV-2 replication. Pharmacological inhibition of NRF-2, and knockdown of NRF-2 and its target genes reduced JQ-1-mediated inhibition of SARS-CoV-2 replication. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variant, which exhibited resistance to JQ-1 and increased sensitivity to exogenously administered type I interferon (IFN-I), suggesting a minimised need for SARS-CoV-2 ORF6-mediated repression of IFN signalling in the presence of JQ-1. Importantly, JQ-1 exhibited a transient antiviral activity when administered prophylactically in human airway bronchial epithelial cells (hBAECs), which was gradually subverted by SARS-CoV-2, and no antiviral activity when administered therapeutically following an established infection. We propose that JQ-1 exerts pleiotropic effects that collectively induce an antiviral state in the host, which is ultimately nullified by SARS-CoV-2 infection, raising questions about the clinical suitability of the iBETs in the context of COVID-19.

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1011657

DOI: 10.1371/journal.ppat.1011657.g001

DOI: 10.1371/journal.ppat.1011657.g002

DOI: 10.1371/journal.ppat.1011657.g003

DOI: 10.1371/journal.ppat.1011657.g004

DOI: 10.1371/journal.ppat.1011657.g005

DOI: 10.1371/journal.ppat.1011657.g006

DOI: 10.1371/journal.ppat.1011657.g007

DOI: 10.1371/journal.ppat.1011657.g008

DOI: 10.1371/journal.ppat.1011657.s001

DOI: 10.1371/journal.ppat.1011657.s002

DOI: 10.1371/journal.ppat.1011657.s003

DOI: 10.1371/journal.ppat.1011657.s004

DOI: 10.1371/journal.ppat.1011657.s005

DOI: 10.1371/journal.ppat.1011657.s006

DOI: 10.1371/journal.ppat.1011657.s007

DOI: 10.1371/journal.ppat.1011657.s008

DOI: 10.1371/journal.ppat.1011657.s009

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2023

detail.hit.zdb_id: 2205412-1

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Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults

van der Boor, Saskia C ; Smit, Merel J ; van Beek, Stijn W ; [et al.]

Elsevier BV ; 2022

In: The Lancet Infectious Diseases Vol. 22, No. 11 ( 2022-11), p. 1596-1605

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In: The Lancet Infectious Diseases, Elsevier BV, Vol. 22, No. 11 ( 2022-11), p. 1596-1605

Type of Medium: Online Resource

ISSN: 1473-3099

URL: Article

DOI: 10.1016/S1473-3099(22)00428-5

Language: English

Publisher: Elsevier BV

Publication Date: 2022

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Prospective Evaluation of Imaging Procedures for the Detection of Pancreaticoduodenal Endocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1

Langer, Peter ; Kann, Peter H. ; Fendrich, Volker ; [et al.]

Springer Science and Business Media LLC ; 2004

In: World Journal of Surgery Vol. 28, No. 12 ( 2004-12), p. 1317-1322

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In: World Journal of Surgery, Springer Science and Business Media LLC, Vol. 28, No. 12 ( 2004-12), p. 1317-1322

Type of Medium: Online Resource

ISSN: 0364-2313 , 1432-2323

URL: Article

DOI: 10.1007/s00268-004-7642-7

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2004

detail.hit.zdb_id: 1463296-2

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Versorgung von Kindern und Jugendlichen mit Geschlechtsdysphorie im Rahmen einer interdisziplinären Spezialsprechstunde

Nieder, Timo Ole ; Preuss, Wilhelm F. ; Becker, Inga ; [et al.]

Brill Deutschland GmbH ; 2014

In: Praxis der Kinderpsychologie und Kinderpsychiatrie Vol. 63, No. 6 ( 2014-07-01), p. 465-485

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In: Praxis der Kinderpsychologie und Kinderpsychiatrie, Brill Deutschland GmbH, Vol. 63, No. 6 ( 2014-07-01), p. 465-485

Type of Medium: Online Resource

ISSN: 0032-7034 , 2196-8225

URL: Article

DOI: 10.13109/prkk.2014.63.6.465

RVK:

XA 10000

RVK:

CL 1000

Language: German

Publisher: Brill Deutschland GmbH

Publication Date: 2014

detail.hit.zdb_id: 2404385-0

detail.hit.zdb_id: 123711-1

SSG: 2,1

SSG: 5,2

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Combined BCL-2 and PI3K/AKT Pathway Inhibition in KMT2A-Rearranged Acute B-Lymphoblastic Leukemia Cells

Holz, Clemens ; Lange, Sandra ; Sekora, Anett ; [et al.]

MDPI AG ; 2023

In: International Journal of Molecular Sciences Vol. 24, No. 2 ( 2023-01-10), p. 1359-

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In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 2 ( 2023-01-10), p. 1359-

Abstract: Numerous hematologic neoplasms, including acute B-lymphoblastic leukemia (B-ALL), are characterized by overexpression of anti-apoptotic BCL-2 family proteins. Despite the high clinical efficacy of the specific BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), dose limitation and resistance argue for the early exploration of rational combination strategies. Recent data indicated that BCL-2 inhibition in B-ALL with KMT2A rearrangements is a promising intervention option; however, combinatorial approaches have not been in focus so far. The PI3K/AKT pathway has emerged as a possible target structure due to multiple interactions with the apoptosis cascade as well as relevant dysregulation in B-ALL. Herein, we demonstrate for the first time that combined BCL-2 and PI3K/AKT inhibition has synergistic anti-proliferative effects on B-ALL cell lines. Of note, all tested combinations (venetoclax + PI3K inhibitors idelalisib or BKM-120, as well as AKT inhibitors MK-2206 or perifosine) achieved comparable anti-leukemic effects. In a detailed analysis of apoptotic processes, among the PI3K/AKT inhibitors only perifosine resulted in an increased rate of apoptotic cells. Furthermore, the combination of venetoclax and perifosine synergistically enhanced the activity of the intrinsic apoptosis pathway. Subsequent gene expression studies identified the pro-apoptotic gene BBC3 as a possible player in synergistic action. All combinatorial approaches additionally modulated extrinsic apoptosis pathway genes. The present study provides rational combination strategies involving selective BCL-2 and PI3K/AKT inhibition in B-ALL cell lines. Furthermore, we identified a potential mechanistic background of the synergistic activity of combined venetoclax and perifosine application.

Type of Medium: Online Resource

ISSN: 1422-0067

URL: Article

DOI: 10.3390/ijms24021359

Language: English

Publisher: MDPI AG

Publication Date: 2023

detail.hit.zdb_id: 2019364-6

SSG: 12

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